Methods and apparatus for delivery of ocular implants

ABSTRACT

An apparatus and methods for delivering ocular implants or microimplants. The apparatus is ergonomically designed for ease of use, and a simple manual depression of an actuator produces proportional movement of a linkage causing the implant or microimplant to be ejected through a cannula disposed at the desired location in the eye. Small gauge cannulas are provided for self-sealing methods of delivery.

TECHNICAL FIELD

The present invention relates to methods and apparatus for deliveringsolid or semi-solid materials into the eye. Specifically, the methodsand apparatus can be used to introduce implants containing therapeuticor active agents, including bioerodible implants, into various locationswithin the eye, including the vitreous of the eye.

BACKGROUND ART

A primary difficulty in treating diseases of the eye is the inability tointroduce drugs or therapeutic agents into the eye and maintain thesedrugs or agents at a therapeutically effective concentration in the eyefor the necessary duration. Systemic administration may not be an idealsolution because, often, unacceptably high levels of systemic dosing areneeded to achieve effective intraocular concentrations, with theincreased incidence of unacceptable side effects of the drugs. Simpleocular instillation or application is not an acceptable alternative inmany cases because the drug may be quickly washed out by tear-action oris otherwise depleted from within the eye into the general circulation.Suprachoroidal injections of drug solutions have also been performed,but again the drug availability is short-lived. Such methods make itdifficult to maintain therapeutic levels of drug for adequate timeperiods.

Efforts to address this problem have lead to the development of drugdelivery devices, or implants, which can be implanted into the eye suchthat a controlled amount of desired drug can be released constantly overa period of several days, or weeks, or even months. Many such deviceshave been previously reported. See, for example, U.S. Pat. No.4,853,224, which discloses biocompatible implants for introduction intoan anterior segment or posterior segment of an eye for the treatment ofan ocular condition. U.S. Pat. No. 5,164,188 discloses a method oftreating an ocular condition by introduction of a biodegradable implantcomprising drugs of interest into the suprachoroidal space or pars planaof the eye. See also U.S. Pat. Nos. 5,824,072, 5,476,511, 4,997,652,4,959,217, 4,668,506, and 4,144,317. Other methods include anchoring aplug or tack containing a drug into the sclera of the eye (see, e.g.,U.S. Pat. No. 5,466,233).

Various sites exist in the eye for implantation of a drug deliverydevice or implant, such as the vitreous of the eye, anterior orposterior chambers of the eye, or other areas of the eye includingintraretinal, subretinal, intrachoroidal, suprachoroidal, intrascleral,episcieral, subconjunctival, intracorneal or epicorneal spaces. Whereverthe desired location of implantation, typical methods of implantationall require relatively invasive surgical procedures, pose a risk ofexcessive trauma to the eye, and require excessive handling of theimplant. For example, in a typical method for placement in the vitreous,an incision is made through the sclera, and the implant is inserted intoand deposited at the desired location in the vitreous, using forceps orother like manual grasping device. Once deposited, the forceps (orgrasping device) is removed, and the incision is sutured closed.Alternatively, an incision can be made through the sciera, a trocar canbe advanced through the incision and then the implant can be deliveredthrough the trocar. Similar methods can be employed to deliver implantsto other locations, e.g., implantation in the anterior chamber of theeye through an incision in the cornea.

The drawbacks of such techniques for implant delivery are many-fold.Extensive handling of the implant is necessitated in these techniques,creating a risk that the implant will be damaged in the process. Manysuch implants are polymer-based and are relatively fragile. If portionsof such implants are damaged and broken-off, the effective therapeuticdose delivered by the implant once placed will be significantly altered.In addition, it becomes inherently difficult using these methods toachieve reproducible placement from patient to patient. Also of importis that fact that all such techniques require an incision or puncture inthe eye large enough to require suturing. Thus such techniques aretypically performed in a surgical setting.

There thus remains a need for a more facile, convenient, less invasive,and less traumatic means for delivering implants into the eye. Therealso remains a need for a more controlled means of delivering implantsinto the eye.

SUMMARY OF THE INVENTION

The present invention meets these and other needs and provides methodsand apparatus for easily, safely, and more precisely delivering animplant into the eye.

In one aspect of the invention, an apparatus is provided having anelongate housing with a cannula extending longitudinally from thehousing. The cannula includes a lumen extending through the length ofthe cannula, such that an ocular implant can be received within thecannula lumen. A plunger having a push rod is also received within thecannula lumen and is capable of movement from a first to second positionwithin the lumen. A linkage is provided having a moveable end engageablewith the plunger, and a fixed end secured to the housing. The moveableend of the linkage is capable of movement from a first to secondposition relative to the housing upon application to the linkage of aforce normal to the housing axis. When such a force is applied theplunger moves from the first to the second position within the cannula,forcing an implant retained within the cannula to be ejected.

In one embodiment, the apparatus further includes an actuating leverwith one end pivotally mounted within mounted the housing and the otherend of the lever engaged with the linkage. The actuating lever canfurther be configured for manual accession, such that manual depressionof the lever against the linkage provides the force normal to thehousing axis which causes translational motion of the moveable end ofthe linkage along the housing axis and subsequent movement of theplunger and ejection of the implant. The linkage itself can furtherinclude a series of flexibly joined segments.

In another embodiment, the apparatus includes a linkage that includesone or more flexible bow elements. The bow element or elements canfurther include a portion or portions that extend from the housing formanual accession, such that manual depression of the portion or portionsprovides the normal force to the housing axis to cause translationalmotion of the linkage.

In a further embodiment, the apparatus includes an actuating leveroperably linked to a linkage comprising a cam assembly. The actuatinglever can be oriented for movement in a direction normal to the housingaxis and can be further configured for manual accession. Manualdepression of the lever causes rotation of the cam assembly about afixed pivot point resulting in engagement of the cam assembly with theplunger and subsequent movement of the plunger to eject the implant.

In yet another embodiment, the cannula is further configured to have anouter diameter of 0.032 inches or less. In further embodiments, thecannula is configured to have an outer diameter of 0.028 inches or lessor 0.025 inches or less. Alternatively, in cases where the cannula has anon-circular cross-section, the cannula can have a cross-sectional areaof up to 0.0008 square inches or more, depending on the particularcross-sectional geometry. Cannulas having such configurations are ableto receive and deliver smaller ocular implants, i.e., so-calledmicroimplants.

The invention also provides methods of delivery of an implant to alocation of the eye. Various sites exist in the eye for implantation ofa drug delivery device or implant, such as the vitreous of the eye,anterior or posterior chambers of the eye, or other areas of the eyeincluding intraretinal, subretinal, intrachoroidal, suprachoroidal,intrascleral, episcleral, subconjunctival, intracorneal or epicornealspaces. In one aspect of the invention, a cannula is used having anouter diameter of 0.032 inches or less. In other aspects of theinvention, a cannula is used having an outer diameter of 0.028 inches orless or 0.025 inches or less. In yet another aspect of the invention, incases where the cannula has a non-circular cross-section, the cannulahas a cross-sectional area of up to 0.0008 square inches or more,depending on the particular cross-sectional geometry. The use ofcannulas having such cross-sectional dimensions allows for self-sealingmethods of implant delivery.

Accordingly, in one embodiment, a method of delivering an ocularmicroimplant into a patient's eye is provided which involves providing acannula having a distal sharpened tip, lumen extending through thecannula, a microimplant that can be retained within the lumen, and apush rod that can be received through a proximal end of the cannula. Thecannula is then used to puncture through the outer layer of a patient'seye with the cannula and inserted to a desired location within thepatient's eye or is otherwise advanced to a desired location in apatient's eye. Once the cannula is positioned, the push rod is movedfrom the proximal end of the cannula toward the distal end of thecannula, thereby ejecting the microimplant from the cannula. Afterejection, the cannula and push rod are removed from the patient's eye.In certain aspects, where cannulas having particular cross-sectionalgeometries are used, the puncture created by the insertion of thecannula into the patient's eye is self-sealing upon the removal of thecannula. Particular orientations of the cannula during insertion can aidin self-sealing. The cannula tip can further be configured to haveparticular beveled designs which further aid in the self-sealing method.Alternatively, methods of delivery are also contemplated where theresultant puncture is not self-sealing but can be sealed using knownmethods.

While the delivery apparatus according to the invention facilitates theinventive method of delivering an ocular microimplant, it is notnecessary to the practice of inventive method. For example, one skilledin the art can also use a needle and plunger assembly, where the needlehas dimensions corresponding to the described cannula.

The methods and apparatus of the invention provide numerous advantages,not least of which is providing for an easier, convenient, and lesstraumatic means for delivering implants into the eye. In certainembodiments, the self-sealing means of implant delivery can be achieved,which in addition to being less invasive and traumatic, offers lesscostly treatment by obviating the need for performing the procedure in asurgical setting.

The methods and apparatus of the invention also provide for a morecontrolled means of delivering implants into the eye. In particular,embodiments of the inventive apparatus are designed to provide a smooth,controlled delivery of the implant. Additional embodiments provide forsafety features which include, among other things, user feedback uponthe ejection of an implant and locking mechanisms which prevent backflowof eye fluid after ejection and/or which also prevent reuse of theapplicator. Another advantage of the inventive apparatus is ease andflexibility of manufacture and assembly of apparatuses for delivery ofdifferent implants.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a side view of an implant delivery apparatus according toone embodiment of the present invention;

FIG. 2 depicts a top view of the apparatus of FIG. 1;

FIG. 3 depicts a front view of the apparatus of FIG. 1;

FIG. 4 depicts a perspective exploded view of the apparatus of FIG. 1,showing the nose cone disengaged from the housing;

FIG. 5 depicts a perspective exploded view of the nose cone and cannulaassembly of the apparatus of FIG. 1;

FIG. 6 depicts a perspective exploded view of the housing, linkage, andactuating lever of the apparatus of FIG. 1;

FIG. 7 depicts an enlarged perspective view of the linkage of theapparatus of FIG. 1;

FIG. 8 depicts an enlarged perspective view of the actuating lever ofthe apparatus of FIG. 1;

FIG. 9A depicts a side elevated view in section of the apparatus of FIG.1, showing the linkage, actuating lever and cannula assembly prior toejection of an implant from the apparatus;

FIG. 9B depicts a side elevated view in section of the apparatus of FIG.1, showing the linkage, actuating lever and cannula assembly afterejection of an implant from the apparatus;

FIG. 10 depicts a perspective exploded view of an implant deliveryapparatus according to another embodiment of the invention, showingdifferent housing, linkage and cannula assemblies;

FIG. 11A depicts a side elevated view in section of the apparatus ofFIG. 10, showing the linkage and cannula assembly prior to ejection ofan implant from the apparatus;

FIG. 11B depicts a side elevated view in section of the apparatus ofFIG. 10, showing the linkage and cannula assembly after ejection of animplant from the apparatus;

FIG. 12A depicts a side elevated view in section, with parts brokenaway, of an implant delivery apparatus according to yet anotherembodiment of the invention, showing yet another linkage mechanism andcannula assembly prior to ejection;

FIG. 12B depicts a side elevated view in section of the apparatus ofFIG. 12A, with parts broken away, showing the linkage and cannulaassembly after ejection of an implant from the apparatus;

FIGS. 13A-B depict top and side views, with parts broken away, of acannula tip according to one embodiment of the invention;

FIGS. 14A-B depict top and side views, with parts broken away, of acannula tip according to another embodiment of the invention; and

FIG. 15 depicts a side section view, with parts broken away, of acannula according to another embodiment of the invention, showing meansfor retaining an implant within the cannula.

DETAILED DESCRIPTION

An embodiment of an implant delivery apparatus according to the presentinvention is depicted in FIGS. 1-9. As shown, implant delivery apparatus10 includes external housing 20 with nose cone 30 attached to andextending from the housing. Cannula 40, having beveled tip 41, extendsfrom the nose cone. Ejector button 50 extends through opening 52 of thehousing. As described further herein, an implant can be loaded into thecannula and the apparatus can be readily manipulated to introduce thecannula into a patient's eye at a desired location. Depression of theejector button actuates the apparatus, and causes the ejection of theimplant into the patient's eye.

As used herein, “implants” refers to ocular implants or drug deliverydevices which can be implanted into any number of locations in the eye,and which are designed such that a controlled amount of desired drug ortherapeutic can be released over time. Such implants, which can be solidor semi-solid, are biocompatible, and in many but not all cases areformed of a bioerodible substance, such as a bioerodible polymer.“Microimplants” refers to implants having a sufficiently smallcross-sectional area that they can be delivered by methods and/orapparatus according to the invention that result in self-sealing of theeye at the puncture site associated with the delivery. In particular,such microimplants have dimensions such that they are deliverablethrough 21 gauge or 22 gauge or smaller gauge cannulas. Thin wallversions of 21 gauge needles can be manufactured having inner diametersof up to 0.028 inches, thus cylindrical microimplants deliverablethrough such sized cannulas will have outer diameters of less than 0.028inches. Thin wall versions of 22 gauge needles can have inner diametersof up to 0.023 inches, and thus cylindrical microimplants with diametersof less than 0.023 inches will be deliverable through such sizedcannulas. Microimplants can also have non-circular cross-sectionalgeometries for delivery through cannulas having correspondingcross-sectional geometries. Where the micro-implant has non-circularcross-section, the cross-sectional area may be up to 0.00025 squareinches or more, depending on the particular cross-sectional geometry.

As used herein, “self sealing” methods of delivering microimplants intothe eye refers to methods of introducing microimplants through a cannulaand into desired locations of a patient's eye without the need for asuture, or other like closure means, at the cannula puncture site. Such“self sealing” methods do not require that the puncture site completelyseal immediately upon withdrawal of the cannula, but rather that anyinitial leakage is minimum and dissipates in short order such that asurgeon or another equally skilled in the art, in his or her goodclinical judgment, would not be compelled to suture or otherwise provideother like closure means to the puncture site.

The apparatus is ergonomically configured for easy gripping andmanipulation, and has a general overall shape similar to a conventionalpen or other writing instrument. The apparatus will typically be graspedby the user between the thumb and the middle finger. Tactile ridges 22are provided on the housing, in the areas around the ejector buttonwhere the thumb and middle finger of the user are contact the apparatus,to provide a more secure grip and feel to the user. Ejector button 50itself is provided with tactile grooves 53 on the button surface wherethe index finger typically contacts the button, also providing for amore secure grip and feel for the user.

As shown more clearly in FIG. 4, nose cone 30 can be manufactured as aseparate piece that is then secured to the housing. Specifically, collar24 extends from the housing as shown. Nose cone 30 is configured forreceipt over and attachment to the collar.

As seen in FIG. 5, nose cone 30 receives cannula assembly 42 whichconsists of cannula 40 and cannula hub 44. The hub is configured forreceipt and securement within nose cone 30, with cannula 40 extendingthrough nose cone hole 32. The cannula lumen is in communication withinner passageway 43 of the hub, such that implant 1 can be passedthrough the inner passageway of the hub and loaded into the cannulalumen. Plunger 46 includes push rod 48 and cone 49. Push rod 48 isconfigured for slidable receipt within the cannula lumen, and is ofsufficient length to displace a loaded implant retained with the cannulalumen and eject it from the cannula tip.

Referring to FIG. 6, it can be seen that housing 20 is formed of twohalf sections 21 and 22. These sections are preferably configured tosnap-fit together, although other known methods of attaching the twohalves together are contemplated, including, e.g., gluing, welding,fusing, etc. Alternatively, the housing could be singularly molded.Label plate 23 is also provided, which likewise can be snapped onto orotherwise secured to, the housing. Nose cone 30 can be secured to collar24 of housing 20 by similar means.

Actuating lever 52 and linkage 60 are retained within housing 20. Asseen in FIGS. 6 and 8, actuating lever 52 consists of elongate member 54having pins 55, 56 extending from the member at one end and ejectorbutton 50 extending from the other end. Pins 55, 56 extend along acommon axis and are received in corresponding pivot holes 26 of thehousing sections, such that when assembled, the lever can pivot aboutthe pins in a restricted range of motion within the housing.

Linkage 60, as seen more clearly seen in FIG. 7, consists of front andrear blocks 61 and 62, with a plurality of joined segments 63 extendingtherebetween. The segments are sequentially joined to one another.Flexible joints 64 connect the segments to each other and to the frontand rear blocks. The linkage is flexible yet resilient, and preferablyformed of a contiguous, moldable plastic piece. Portions of the linkagehaving a relatively thin cross-sectional area of material form flexiblejoints 64, and disposed between thicker, less flexible segments 63. Thisallows for flexure of the linkage at the joint locations when a force isapplied to the linkage. Other known materials are also suitable for thelinkage, including e.g. shape memory alloys, provided the resultantlinkage is capable of lengthwise extension when a force normal to orperpendicular to the length of the linkage is applied.

When assembled, rear block 62 is fixedly secured into slot 27 of thehousing, as shown in FIG. 6, and more clearly in FIGS. 9 and 10. Guidepins 65, 66 extend from front block 61 and are received in guide track28. Guide track 28 is defined by guide ribs 29, 29 that extend inwardlyfrom collar 24. Cone 49 of plunger 46 abuts against front block 61 ofthe linkage. Alternatively, the linkage-plunger assembly can beintegrally formed as a single unit. The linkage, guide track, plunger,cannula, and implant (if loaded within the cannula) are all alignedalong the longitudinal axis of the apparatus.

As can be seen, the underside of button 50 of actuating lever 52 is incontact with the linkage (FIG. 9A). In operation, depression of button50 by the user transmits force against the linkage through underside ofbutton 50 in a direction generally normal to the longitudinal axis ofthe apparatus. This force is transmitted through the linkage, and isconverted into a longitudinal force along the longitudinal axis of theapparatus, through flexure of the linkage joints. Because the rear blockend of the linkage remains fixed to the housing, this action results intranslational motion of the free, front block end of the linkage in thedirection away from the fixed rear block of the linkage. Thistranslational movement of the front block of the linkage in turn pushespush rod 46 through the lumen of cannula 40. Where an implant is loadedand retained within the cannula lumen, the motion of the push rod inturn ejects the implant from the cannula tip (FIG. 9B).

Button 50 also includes tab 57, which is engageable with tab slot 58 ofthe housing. The tab includes a detent which, when engaged in slot 58will provide an audible click, signaling the user that the implant hasbeen deployed, and will also retain the actuating lever in a locked,depressed condition, after deployment of the implant.

A second embodiment of an implant delivery apparatus according to thepresent invention is depicted in FIGS. 10-11. In this embodiment,implant delivery apparatus 110 includes housing 120 with actuator 170disposed within the housing. The actuator includes linkage 160 formed oftwo opposing flexible bowing elements 165 and 166. Ridges 171 and 172are provided on the apexes of the bowing elements, and portions of thebowing elements that include ridges 171 and 172, extend through openings124 and 125 of the housing. Cannula assembly 142 is secured to thehousing. As with the previous embodiment, an implant can be likewiseloaded into the cannula. Depression of bowing elements 165 or 166actuates the apparatus, causing the ejection of the implant from thecannula, as will be further detailed.

Housing 120 is formed of two sections, upper and lower housing sections121 and 122, that can be assembled as previously described above withrespect to the embodiment of FIGS. 1-9. Similarly, apparatus 110 is alsoergonomically configured for easy gripping, and will likewise typicallybe grasped by the user between the thumb and the middle finger. Ridges171 or 172 include tactile grooves or are otherwise textured to providefor a more secure grip and feel for the user. Additional tactile ridgescan be provided on the housing itself in proximity to openings 125 and126.

Linkage 160 further includes front and rear blocks 161 and 162, and pushrod 148 extending from the front block 161. The ends of bowing elements165 and 166 coincide at front and rear blocks 161 and 162. Suitablematerials for linkage 160 are the same as those describe above withrespect to linkage 60 of the embodiment of FIGS. 1-9. When assembled,rear block 162 is secured to the housing and retained in a fixedposition relative to the housing by tabs 127 and 128. Front block 161 isreceived and slidable within track 129 on lower housing section 122.Push rod 148 extends from front block 161 and is axially aligned withcannula 140. The push rod can be formed of wire, and in one method ofmanufacture, the linkage can be molded directly onto a wire and then thewire can be cut to the desired dimensions to form the push rod.

In the undeployed condition, depicted in FIG. 11A, implant 101 isretained in the cannula, distal to the push rod. Manual pressure onbowing element 165 or 166 supplies a normal force to longitudinal axisof the apparatus. This force is transmitted, via flexing of the bowingelements, into a longitudinal force along the longitudinal axis, whichin turn causes movement of the free, front block 161 of the linkage awayfrom the fixed, rear block 162. This in turn pushes push rod 146 throughthe cannula, which in turn ejects a loaded implant from the cannula, asshown in FIG. 1B.

Lock tab 174 is provided on upper housing section 121 and furtherincludes lock stop 175 that is engageable with notch 176 on front block161. The lock tab itself can be integrally formed with upper housingsection 121, and configured such that the lock stop snap-fits into thenotch when positioned properly. In operation, as front block 161 movesforward in relation to the housing, angled face 178 engages lock stop175 and deflects the lock tab upward. The lock tab remains deflectedupward until movement of the front block brings notch 176 into positionsuch that lock stop engages the notch. As can be appreciated, thelocation of the notch relative to the front block length will govern thedistance traveled by the push rod in ejecting the implant. In theembodiment shown, the actuator can be inserted into the housing in twodifferent orientations to provide for two different ejection distancesfor the push rod. As seen, a similar angled face 179 and notch 177 areprovided on block 161 opposite face 178 and notch 176, with notch 176being offset from notch 177 relative to housing longitudinal axis.Therefore, the same actuator can be rotated 180 degrees upon assembly ofthe apparatus such that lock stop 175 instead engages notch 177, therebyallowing for the push rod to travel an alternate distance govenrnedinstead by the location of notch 177 relative to the front block length.In the embodiment shown, notch 177 provides for a 1 mm displacement andnotch 176 provides for a 2 mm displacement.

A third embodiment of an implant delivery apparatus according to thepresent invention is depicted in FIGS. 12A-12B. In this embodiment,implant delivery apparatus 210 includes housing 220 and cannula assembly242. Cannula assembly 242 includes cannula 240 disposed within andextending from nose portion 230, and push rod 248 that is slidablyreceived with the cannula and terminates at its proximal end in cone 249which is disposed in the interior of the housing. Lever 254 is mountedfor movement normal to the longitudinal axis of the apparatus. One endof the lever extends from the apparatus through opening 251 andterminates in button 250. The other end of the lever includes tab 257which is engageable with latch 258 on housing 220. The tab and latch canbe configured to engage in a snap-fit relationship. Cam 260 is disposedwithin housing 220 and is pivotally mounted to the housing about pivot265 which is located distally relative to lever 254. Slot 267 isprovided on cam 260. Pin 256 on lever 254 is slidably retained withinslot 267. The end of cam 260 is located proximal to the cone 249 andpush rod 248 assembly.

In the undeployed condition depicted in FIG. 12A, implant 201 isretained in the cannula distal to the push rod. Manual depression ofbutton 250 causes downward movement of lever 254 normal to thelongitudinal axis of the apparatus. This movement exerts a force ontocam 260 which is transmitted by way of pin 256 of the lever to slot 267of the cam, causing rotational movement of cam about pivot 265. With theend of cam 260 in approximation to cone 249, such rotation of the camcauses the end of the cam to engage cone 249, causing translationalmovement of cone 249 and plunger 248 relative to the housing. Thistranslational movement of the plunger, in turn, ejects the implant fromthe cannula, as depicted in FIG. 12B. When the lever is fully depressedand the implant ejected, tab 257 engages latch 258, thereby locking theassembly into a depressed, post-ejection, condition.

An advantage of an implant delivery apparatus according to the inventionis that it provides for a very smooth, controlled ejection of theimplant. By “controlled” it is meant that the force applied to theimplant for ejection is proportional to the force applied by the user toactuate the apparatus. The user has direct feedback as to the rate ofejection and can dynamically adjust the force being delivered to thelinkage to obtain the desired ejection rate. In addition, depending inparticular linkage configurations and dimensions, the apparatus can beconfigured such that the range of translational movement of the plungeralong the longitudinal, or “x” axis, of the housing can be significantlylonger, although still proportional to, the range of movement of theactuator along the normal or “y” axis. In such situations, relativelylong implants can be effectively delivered by an apparatus that isactuated by a comparatively short actuating stroke. The embodiment ofFIGS. 9A & 9B depicts such a situation, where the displacement y ofbutton 50 results in a larger displacement x of plunger 48.

The controlled delivery that can be achieved by the inventive apparatushas additional advantages as well. For example, the controlled deliveryprovides a more predictable and reproducible placement of the implant,i.e., the implant will tend to be placed at a location very near thecannula tip, and not be projected to a more distant location as maypotentially occur with the use of, e.g., a spring-loaded device where asudden force is instantaneously applied to the implant. The inclusion oflocking mechanisms, such as tab 57 and slot 58 locking mechanism of theapparatus of FIGS. 1-9, or the lock tab mechanism of the apparatus ofFIGS. 10-11, or the tab-latch mechanism of the apparatus of FIGS.12A-12B, guards against backflow of eye fluid into the cannula afterdeployment of the implant. These locking mechanisms can further beconfigured such that the engagement between the two is irreversible,which prevents reuse of the apparatus. This is advantageous, e.g., if asingle-use apparatus is desired.

The combination of the overall housing shape, together with theparticular positioning of the tactile ridges in approximation with theactuator position also provides for additional safety advantages. Inparticular, the design allows the user to control the positioning of thecannula and maintain its stability primarily through manipulation of thethumb and middle finger. The index finger meanwhile controls actuationof the apparatus, and thus the ejection of the implant from the cannulaat the desired location. This design effectively separates positioningcontrol from actuation control, and reduces the risk that the step ofejecting the implant will inadvertently cause movement of the devicesuch that the actual placement of the implant is not at the intendedlocation.

The cannulas themselves are in many respects is similar to standardsurgical needles, and can be formed of stainless steel in a variety ofgauges. The gauge will be chosen such that the inner diameter of thecannula lumen, or bore, will correspond to the outer diameter of thechosen implant, with enough tolerance such that the implant can bereceived into and subsequently ejected from the cannula lumen. In theembodiment of FIGS. 10 and 11, cannula 140 can be a standard surgicalneedle having luer lock fitting on its hub, which can be received andsecured to a corresponding luer fitting provided on the end of housing120.

It is desirable, although not necessary, to use a cannula thatcorresponds in dimensions to a 21 or 22 gauge needle or smaller. Such asmall cannula has the important advantage that punctures made by suchsmall bore needle or cannula according to techniques described hereinare self-sealing. In the present application, this becomes advantageousin that the implant delivery into the eye can be accomplished withoutthe need for suturing the puncture site, as would be necessary were alarger gauge needle used. We have determined that by using a 21 or 22gauge cannula or smaller, the implant can be placed and the cannulawithdrawn without excessive fluid leakage from the eye, despite thenormal fluid pressures within the eye, and stitching of the puncturesite can be avoided. 21 gauge needles have outer diameters ofapproximately 0.032 inches. Thin wall or extra thin wall versions of 21gauge needles can have inner diameters of approximately 0.023 to 0.026inches. 22 gauge needles have outer diameters of approximately 0.028inches, and thin wall or extra thin wall versions of 22 gauge needleshave inner diameters of approximately 0.019 to 0.023 inches. Ideally acannula corresponding in dimensions up to those of 22 or 23 gauge, thinwall needles are used. Microimplants are dimensioned to have outerdiameters to be received within the needle cannulaes with sufficienttolerances to be readily pushed through the cannula. For example andwithout being so limited, microimplants with a diameter of 0.018 inchescan be easily delivered through a 22 gauge thin wall needle, and amicroimplant with a diameter of 0.015 inches is easily deliverablethrough a 23 gauge thin wall needle. The invention further contemplatesthe use of cannulas having non-circular cross-sections, including ovalor elliptical cross-sections. For such non-circular cross-sectionalcannulas, it is desirable that the cross-sectional area correspond tothat of a circular cannula having up to a 0.032 inch diameter, that is,a cross-sectional area up to 0.0008 square inches or more, depending onthe particular cross-sectional geometry.

In addition to cannula dimensions, additional modifications to both thecannula tip and in particular methods of insertion can further aidsuccessful self-sealing methods of implantation. A typical problem wheninserting a cannula into any tissue is the phenomena of “coring” of thetissue, where the insertion actually cuts a cylindrical section oftissue that enters the cannula lumen. Such coring when it occurs in theeye can exacerbate leakage of eye fluid through the injection site. Byapproaching the eye tissue at more of an angle relative to normal, thereis a better opportunity for the cannula tip to penetrate and separatethrough the tissue layers and reduce coring of the tissue. Additionaltechniques to further reducing coring and/or excessive leakage arefurther described herein.

The cannula tip itself also can be configured to reduce coringphenomena, for instance, by sharpening certain portions of the bevel tipand dulling others. FIGS. 12A and 12B depict one such embodiment, wherecannula tip 40 a includes side bevels 31 a, 32 a that extend distally ofdesignated line L1 and constitute approximately one half of the beveltip and dulled area 33 a extending proximally of line L1, constitutingthe other half of the bevel tip. The dulled area 33 a can be createdthrough conventional polishing techniques known in the art. FIGS. 13Aand 13B depict another such embodiment, where cannula tip 40 b that alsoincludes side bevels 31 b and 32 b extending distally of designated lineL2 and dulled area 33 b extending proximally of line L2. However, inthis embodiment, the side bevels 31 b, 32 b constitute only about onequarter or less of the bevel tip. In each of these embodiments, thesharp side bevels allow for an initial piercing of tissue, but as thetip is further inserted the tissue encounters the dulled areas of thebevel tip, which do not have sharp cutting edges, thus promotingseparation of tissue layers as the cannula is advanced and mitigatingagainst further cutting and possible coring of the tissue. In additionto these designs, conventional needle tips have also provensatisfactory.

One skilled in the art will appreciate that the particular site of entryand the distance the cannula is inserted will depend on the particularapplication and the desired final location of the implant. As can alsobe appreciated, the ability provided herein to provide for aself-sealing method for delivering implants, has enormous impact on theability of physicians and healthcare workers to treat diseases of theeye, because it obviates in most situations the necessity of surgeryfacilities, and accompanying surgical support, currently required byconventional methods.

To administer an implant using, e.g., the implant delivery apparatus ofFIGS. 1-9, the user can grasp apparatus 10 between the thumb and middlefinger along tactile ridges 22, and position the apparatus near thedesired point of entry into the patient's eye. The patient typicallywill be under a topical or local anesthetic. The user can then advancecannula 40 into the patient's eye to the desired depth, and depressejector button 50 to eject the implant at the desired location. Thecannula 40 is then withdrawn. Specific techniques for cannulaadvancement, including angles of orientation of the cannula and thebevel are further discussed herein. Where cannula 40 is dimensioned toreceive and retain a microimplant, as previously discussed, theresultant puncture site can self-seal upon withdrawal of the cannula.Otherwise, in situations where a larger cannula and implant are used,the puncture site can be closed up by known methods, such as suturing.

Methods of delivering implants, including self-sealing methods, can alsobe performed without the inventive apparatus, albeit less conveniently.In such self-sealing methods, a cannula having dimensions correspondingto those described above can be provided attached to a suitable holder,such as, e.g., a typical needle and syringe assembly. The microimplantis loaded and retained within the cannula lumen, and a push rod isfurther provided with the distal end received through the proximal endof the cannula lumen and positioned adjacent the microimplant. Thedistal end of the push rod remains outside the cannula and manuallyaccessible. This assembly is then brought into position near thepatient's eye, and the cannula is then used to puncture through theouter layer of a patient's eye and the cannula is further advanced adesired location within the patient's eye for deposition of themicroimplant. Once the cannula is positioned, the push rod is moved fromthe proximal end of the cannula toward the distal end of the cannula,thereby ejecting the microimplant from the cannula. After ejection, thecannula and push rod are withdrawn from the patient's eye, and thepuncture created by the insertion of the cannula into the patient's eyeis self-sealing upon the removal of the cannula. Alternatively, similarmethods can be employed using cannulas having other dimensions, wherethe resultant puncture is not self-sealing but can be sealed using knownmethods.

For placement e.g. in the vitreous cavity of the eye, usefulimplantation methods include advancing the needle through the pars planaat a location approximately 3.5-4 mm from the limbus of the eye. Forsmaller diameter needles, e.g., 25 gauge or smaller, the needle can beinserted from any angle relative to the eye and still produce acceptableself-sealing results. For larger gauge needles, e.g., 23 gauge andabove, self-sealing results can be enhanced by inserting the needle atangle relative to the eye surface. For example, good results areachieved by inserting the angle at an angle of 45° or less relative tothe eye surface. Also, slightly improved results can be seen in somecases by orienting the bevel of the needle downward with respect to theeye surface. Another advantageous method involves a so-called “tunneltechnique” approach. In this technique, the patient's eye is restrainedfrom moving using e.g. a cotton swab or forceps, and the needle isadvanced into the sclera at an angle approaching parallel relative tothe eye surface. In this technique, the bevel will usually be orientedupward with respect to the eye surface. Once the tip is advancedsufficiently far enough into the scleral layer, usually such that thebevel portion is at least disposed within the scleral layer, the angleof the needle is adjusted to a more downward angle into the eye, and theneedle is further advanced. Using such methods, with the shallower angleof insertion, yields wound edges that close up and seal more readily.Without being bound by theory, it is believed that insertion of theneedle by this technique creates a scleral “flap” that, underintraocular pressure of the eye, is forced upward and pressed againstthe wound path to more effectively close up the wound.

In addition, the direction of insertion of the needle relative to thelimbus of eye can have further implications upon the deposition of theimplant in the vitreous cavity. For example, advancement of the needleposteriorally of the limbus or even circumferentially relative to thelimbus usually provides for a suitable and acceptable location fordeposition of the implant. On the other hand, advancement of the needleanteriorally of the limbus requires some caution, as it can lead toplacement of the implant close to the lens of the eye, which may causesome complications.

Implants that are compatible with loading and ejection from apparatusaccording to the present invention can be formed by a number of knownmethods, including phase separation methods, interfacial methods,extrusion methods, compression methods, molding methods, injectionmolding methods, heat press methods and the like. Particular methodsused can be chosen, and technique parameters varied, based on desiredimplant size and drug release characteristics. For microimplantsdescribed herein, which can be delivered through cannulas correspondingto a 21 gauge needle or smaller, and which therefore havecross-sectional diameters of 0.026 inches or less, or similarcross-sectional areas, extrusion methods are particularly useful.Extrusion methods, as well as injection molding, compression molding,and tableting methods, can all achieve the small cross-sectionaldiameters or areas required of microimplants. Extrusion methods also mayresult in more homogenous dispersion of drug within polymer, which canbe important given the small dimensions of microimplants.

As previously mentioned, microimplants that have diameters of 0.018inches or less are deliverable through 22 gauge thin-walled cannulaes,and microimplants with diameters of 0.015 inches or less are deliverablethrough 23 gauge thin-walled cannulaes. Because of the extremely smallcross-sectional diameters or areas of these microimplants, thecorresponding length will need to proportionally larger to providedesired therapeutic dosages of many active agents. Typically, themicroimplants can be manufactured so as to extend up to about 6 or 7 mmin length or longer. A microimplant of 7 mm or less in length may bepreferable, at least for placement in the vitreous, as implants ofgreater length may interfere with a patient's vision.

In manufacturing an implant delivery apparatus according to theinvention, it may be desirable to pre-load the implant into the cannula.Pre-loaded apparatus provide added convenience for the user and avoidunnecessary handling of implants. Further, such loading can be doneunder sterile conditions, thereby ensuring delivery of a sterilizedimplant. For the embodiment of FIGS. 1-9, the implant can be pre-loadedinto the cannula assembly and the loaded cannula assembly incorporateinto the nose cone. In this fashion, loaded nose cone/cannula assembliescan be pre-assembled, for later incorporation with the housing assembly.Similarly, for the embodiment of FIGS. 10-11, the implant can bepreloaded in the cannula and then later assembled onto the housingassembly. In an alternative variation on this embodiment, the cannulacan have two separate parts, with one part of the cannula retainedwithin the housing that then communicates with the other externalportion of the cannula that is subsequently connected to the housing. Insuch a variation, an implant can further be preloaded in the cannulapart retained within the housing. In any case, push rods and linkages ofthe appropriate lengths are provided dependent on the length of theparticular loaded implant, such that complete ejection of the particularimplant can be assured.

Label plates, or other locations on the housing, can include theappropriate information relative to particular implant loaded. Giventhis interchangeability, unique apparatus for the delivery of selectedimplants can be easily manufactured, simply by providing the particularcannula, plunger, and linkage system for the selected implant. Theremaining components of the apparatus remain the same. The name plate orhousing itself can be labeled to correspond to the selected implant,thus identifying the apparatus with the loaded implant.

When the apparatus is assembled with the implant pre-loaded, it mayfurther be desirable that the implant be positioned just proximal of theopening at the cannula tip. In this fashion, the introduction of airinto the eye can be avoided when the implant is ejected, as couldotherwise occur were the implant located further within the cannulalumen and an air bubble or air pocket allowed to exist between thecannula tip and the implant and ejection of the implant were to forcethe air bubble or air pocket into the eye. One method to accomplish thisis to load the implant distally into the cannula followed by theplunger, with the plunger length designed to push the implant to thedesired pre-actuation position. When the cannula assembly is theninstalled onto the housing, the plunger and thus the implant is advancedto the desired position. To guard against inadvertent premature releaseof the implant, the cannula can have a slight bend incorporated into thetip such that enough friction exists between the inner wall of thecannula and the implant to hold the implant in place, but at the sametime, the frictional force is easily overcome by action of the plungerto eject the implant upon actuation of the apparatus.

Other mechanisms to retain the implant within the cannula are alsocontemplated. An example of one such retention mechanism involves theuse of an O-ring which can be deployed so that at least a portion of theO-ring extends into the lumen of the cannula, and be in frictionalcontact with the implant. In this fashion, the implant is held in placewithin the cannula by the O-ring, but again the frictional forceimparted by the O-ring against the implant is easily overcome by theforce imparted by the plunger to eject the implant from the cannula. Inone variation, the O-ring can be disposed within the cannula itself. Inanother variation, shown in FIG. 15, notch 303 is cut across theexterior of cannula 340, where the depth of the notch is such that itreaches into the lumen. That is, the notch is cut into the cannula to adepth where the cannula lumen is in communication with the notch andthus the exterior of the cannula. O-ring 302 is then positioned aroundthe cannula exterior with a section of the O-ring residing in the notch,such that a portion of the O-ring extends into the cannula lumen, and isin frictional contact with implant 301 positioned therein. In thevariation shown, the frictional force applied can be approximately 25-30g, which is easily overcome by typical actuating forces of approximately500 g. The O-ring can be formed of a variety of known materials,including silicone or thermoplastic elastomers. The O-ring can havecircular cross-sections, or in order to provide more contact surfacearea with the implant, it can also have more oblong cross-sections, oroval cross-sections, or even rectangular cross-sections. The inclusionof the O-ring around the exterior of the cannula can also serveadditional purposes. As an example, the provision of the exteriorlocated O-ring provides an easily identifiable depth gauge and depthstop for the user to ensure that the cannula is inserted into thedesired eye location up to but not beyond a specified depth prior toejection of the implant. Alternatively, the cannula itself can besuitably marked to provide easily identifiable depth markings.

Other contemplated retention mechanisms similarly involve deployment orinsertion of a frictional stop into the lumen of the cannula. Forexample, in a variation on the use of O-rings as described above, anotch can likewise be cut into the cannula and the cannula then fittedwith a shrink tubing, such as thin-wall medical grade heat shrinkpolymer tubings, which include but are not limited to e.g. polyolefins,fluoropolymers (PTFE), polyvinyl chlorides (PVC) and polyethyleneterephthalates (PET). Once positioned around the cannula, such tubingscan be caused to shrink both axially and radially, resulting in aportion of the tubing being shrink-fitted through the notch and into thelumen, to create a frictional stop much like the previously describedO-ring variations. In another example, other frictional stops can bedeployed within the cannula, including, e.g., leaf springs, springclips, or other like mechanisms, which would impart a frictional forceagainst a retained implant, yet still allow the implant to be expelledfrom the cannula upon actuation. Still other frictional stops can becreated by manipulation of the cannula itself. For example, similar tothe bending of the cannula described above, a section of the cannula canbe dented or “dimpled” such that there is an indention of the cannulawall within the lumen. Such an indentation can form the frictional stop.

Still other retention mechanisms are contemplated that can rely onbiocompatible adhesives, coatings, or membranes. For example, arelatively weak biocompatible adhesive can be used to coat the implantor the lumen such that the implant adheres to and remains positionedwithin the lumen. Alternatively, the lumen can be coated with apolymeric or other coating that provides additional frictionalresistance to movement of the implant within the lumen. In such cases,the resistance provided by the adhesive or coating will be easilyovercome upon actuation of the delivery device. As another example, athin membrane can be deployed within the lumen that spans the lumendiameter. Such a membrane would have sufficient integrity to resistmovement of the implant within the lumen, but would readily give way orbreak when the actuation force is imparted to expel the implant.

Other cannula designs can likewise achieve the desired effect ofavoiding the introduction of air into the eye upon ejection of theimplant. For example, the implant can be positioned proximally of thecannula tip but with sufficient tolerance between the implant andcannula wall to provide for air exhaust past the implant as it is movedthrough the cannula. Adequate tolerances are those that retain air infront of the implant at close to ambient pressure as the implant ismoved along the cannula. Because fluid pressure within the eye istypically slightly positive relative to ambient pressure, air at ambientpressure will not enter the eye.

Loaded apparatus according to the invention can be packaged to include asafety cap extending over the cannula and securing to the housing. Thiswill provide a measure of safety during handling of the apparatus. Thebutton or other depression mechanism of the apparatus can also include anotch which receives the rim of the safety cap. In this configuration,the safety cap will then also operate to guard against unintentionaldepression of the button or other depression mechanism and ejection ofthe implant.

As can be appreciated, an implant delivery apparatus according to theinvention that is provided loaded with the desired implant is of greatbenefit to the physician user. Such apparatus can be provided sterilepackaged for a single use application. The user need not ever handle theimplant itself. As previously mentioned, the apparatus provides for acontrolled ejection of the implant. The configuration and design of theapparatus also helps to achieve uniform placement of implants frompatient to patient. Further, when the apparatus is configured to delivera micro-implant, the apparatus provides a self-sealing method fordelivery, as previously discussed. This has enormous benefit to thephysician and patient in that the entire implant procedure can safely,easily, and economically be performed in a physician's office, withoutthe need for more costly surgical support currently required for implantdelivery.

The invention is further illustrated by the following non-limitingexamples.

EXAMPLES Example 1 Effects of Needle Size and Technique on VitreousLeakage

Different gauge needles together with various insertion techniques werepursued to determine the maximum size needle gauge and optimum insertiontechnique for mimimum vitreous leakage and “self-sealing” wounds.

Eight rabbits were anaesthetized with a Ketamine/Xylazine cocktail.Drops of a 0.5% Opthaine solution were delivered to each eye of therabbit as a local anaesthetic. 16 g, 20 g, 23 g, 25 g needles(Beckton-Dickinson, Franklin Lakes, N.J.) were attached to syringes andinserted into the vitreous cavities of the rabbits' eyes, through thepars plana (2-3 mm from the limbus) according to varying techniques. Foreach needle size, the needles were inserted at either angles of 90° or45° relative to the pars plana of the eye, or according to the following“tunnel” technique. In the “tunnel” technique, the needle is initiallyadvanced into the first scleral layer of the eye tissue at a veryshallow angle, almost parallel, to the sclera. Once the needle haspenetrated sufficiently, usually to a position whereby the bevel haspassed into the scleral layer, the orientation of the needle is adjustedand further advanced at a sharper angle of attack, for example,typically anywhere up to 45°. Table 1A below details the needle gaugeand insertion technique for each animal. TABLE 1A STUDY DESIGN AnimalEye Needle size Bevel position, insertion orientation 1 OD 16 g Up, 90°OS 16 g Down, 90° 2 OD 20 g Up, 90° OS 20 g Down, 90° 3 OD 22 g Up, 90°OS 22 g Down, 90° 4 OD 23 g Up, 90° OS 23 g Down, 90° 5 OD 25 g Up, 90°OS 25 g Down, 90° 6 OD 23 g Up, 45° OS 23 g Down, 45° 7 OD 23 g Tunneltechnique OS 23 g Tunnel technique 8 OD 22 g Tunnel technique OS 22 gTunnel techniqueOD - right eye,OS - left eye

Upon removal of each needle from the eye, the resulting wounds wereexamined and observations of wound shape and characteristics and amountof vitreous were recorded. The results are tabulated in Table 1B below.TABLE 1B OBSERVATIONS Needle size Bevel position, Observed Wounddescription and Animal Eye (gauge) orientation Leakage characterization1 OD 16   Up, +++ Big, round, not sealing after swab, 90° suture neededOS 16   Down, +++ Big, round, not sealing after swab, 90° suture needed2 OD 20   Up, +++ Big, round, not sealing after swab 90° OS 20   Down,+++ Big, round, not sealing after swab 90° 3 OD 22   Up, +++ Round, notsealing after swab 90° OS 22   Down, + Round, not sealing after swab 90°4 OD 23   Up, ++ Round, not sealing after swab 90° OS 23   Down, +Round, not sealing after swab 90° 5 OD 25 g Up, no leakage Very small,round, sealed after swab 90° − OS 25 g Down, Minimum Very small round,not sealed after 90° ± swab 6 OD 23 g Up, Minimum Almost sealed, 45° ±edges close OS 23 g Down, no leakage Almost sealed, 45° − edges close 7OD 23 g Tunnel no leakage perfectly sealed technique − OS 23 g Tunnel noleakage perfectly sealed technique − 8 OD 22 g Tunnel Minimum sealedtechnique ± OS 22 g Tunnel Minimum sealed technique ±OD - right eye,OS - left eye+++ = severe leakage++ = substantial leakage+ = some amount of leakage+/− = minimum amount of leakage= no leakage

Based on the above and additional observations, it can be concluded thatinsertion technique as well as needle size are important factors indetermining wound characteristics and subsequent wound leakage. For the25 gauge needles, the angle or technique of insertion was lessimportant, with the would be being relatively small, sealed, anddemonstrating minimal to no leakage. For larger gauge needles, insertiontechniques become more important, insertion of the needle at angles lessthan normal, i.e., less than 90°, dramatically reduced the amount ofleakage and the ability of the wound to sealf seal was enhanced.Insertion by the above-described tunnel technique gave the mostpromising results, but even a direct approach at an angle under 45°provides very good results. Additionally, slightly better results wereobtained with the bevel facing downward relative to the eye tissue uponinsertion. Thus it is expected that self-sealing is achievable with 23gauge or larger needles, including 22 and 21 gauge needles, using thedescribed techniques.

Example 2 Delivery Of Microimplants

Cylindrical microimplants having dimensions of 0.015 inches diameter and6 mm length were delivered into posterior segments of rabbits' eyesusing a 23 gauge thin wall needle and according to insertion techniquesdescribed above in Example 1.

Four rabbits were anaesthetized as before with a Ketamine/Xylazinecocktail and with drops of a 0.5% Opthaine solution administered to eacheye of the rabbit as a local anaesthetic. 23 g thin wall needles (BD,Franklin Lakes, N.J.) were attached to syringes and the needle cannulaeswere loaded with the microimplants. The needles were inserted into thevitreous cavities of the rabbits' eyes, according to varying techniquesdetailed in Example 1 and as further described herein. Table 2A belowdetails the needle gauge and insertion technique for each animal. TABLE2A STUDY DESIGN Bevel position, Animal Eye orientation of needle 1 ODUp, 90° OS Down, 90° 2 OD Up, 45° OS Down, 45° 3 OD Up, 45° OS Down, 45°4 OD Tunnel technique OS Tunnel techniqueOD - right eye,OS - left eye

In addition to the angle of insertion and the bevel orientation,different orientations of the needles relative to the limbus of the eyewere also examined for situations where the needle was inserted at anangle other than normal, i.e., 90°. More specifically, the needlesadvanced into the eye in (1) a circumferential fashion, that is, along adirection generally tangential to the limbus, (2) a posterior manner,that is, the needle is advanced generally towards the posterior of theeye, and (3) in an anterior manner where the needle advanced toward theanterior of the eye.

Upon insertion of the needle, the microimplants were delivered into thevitreous cavity of the posterior segment by advancing a push wirethrough the needle cannula to push the microimplants through the needlecannula. The needle was then removed and the resulting wound wasexamined and observations of wound shape and characteristics and amountof vitreous leakage were recorded. The results are tabulated in Table 2Bbelow. Observations were also made as to location and condition of thedelivered implant. TABLE 2B OBSERVATIONS Bevel position, Wound AnimalEye orientation, direction Leakage description DDS disposition 1 OD Up,90° + Round, not quite Adequate sealed after swab OS Down, 90° + Round,not quite Adequate sealed after swab 2 OD Up, 45° ± Almost sealedAdequate circumferentially OS Down, 45° − DDS in the wound, Small piecein the circumferentially after removing wound almost sealed 3 OD Up, 45°− Almost sealed, DDS broken into 2 posteriorly − edges close pieces OSUp, 45° − Almost sealed, DDS touch the anteriorly edges close lens 4 ODTunnel − Sealed Very close to pars Technique plana and anteriorcircumferentially vitreous OS Tunnel − Sealed Very close to parsTechnique plana and anterior circumferentially vitreous+/− = minimum amount of leakage= no leakage

From the above and additional observations it can be expected thatinsertion of the needle at an angle of 45° or less gave satisfactoryresults with respect to self-sealing and likewise resulted insatisfactory placement of the implant. While the previously describedtunnel technique provides for the best self-sealing results, thepositioning of the implant was slightly less controllable than thatobserved by a methods where the needle was advanced along a single path.Also, the orientation of the needle relative to the limbus can beimportant. For example, needles advanced into the eye circumferentiallyor posteriorly provide for a more advantageous deposition of theimplant, whereas needles advanced anteriorly can result in placement ofthe implant close to the lens which may cause complications. Otherdifficulties observed in placement of the implants were caused in oneinstance by breakage of implants during loading such that small piecesof implant were located in the wound. Such occurrences are easilyalleviated through increased care in loading the implant and ensuringthat the push wire is long enough to completely eject the implant.

While preferred apparatus and methods have been described, the skilledartisan will appreciate that obvious modifications can be made that arewithin the scope of the invention, as defined in the appended claims.

1. An apparatus for implanting an ocular implant at a location in apatient's eye, comprising: an elongate housing having a longitudinalaxis; a cannula extending longitudinally from the housing, the cannulahaving a lumen extending therethrough and being configured to receive anocular implant within the cannula lumen; a push rod receivable withinthe cannula lumen and moveable from a first to second position; and alinkage having a moveable end connected to the push rod, and a fixed endsecured to the housing, the moveable end of the linkage being capable ofmovement from a first to a second position relative to the housing uponapplication to the linkage of a force normal to the housing axis,thereby moving the push rod from the first to the second position. 2.The apparatus of claim 1 wherein the moveable end of the linkage iscapable of translational motion along the housing axis.
 3. The apparatusof claim 1 further comprising an ocular implant located within the lumencannula.
 4. The apparatus of claim 3 wherein said implant is amicroimplant.
 5. The apparatus of claim 3 wherein said implant isbiodegradable.
 6. The apparatus of claim 1 further comprising anactuating lever engageable with said linkage.
 7. The apparatus of claim6 wherein the actuating lever is pivotally mounted within said housing.8. The apparatus of claim 6 wherein said actuating lever furtherincludes a button extending from the housing for manual depression ofthe lever.
 9. The apparatus of claim 1 wherein said linkage furthercomprises a plurality of flexibly joined segments.
 10. The appartus ofclaim 1 wherein said linkage further comprises one or more flexible bowelements.
 11. The apparatus of claim 10 wherein a portion of at leastone of the flexible bow elements extends from the housing for manualdepression.
 12. The apparatus of claim 1 wherein said linkage furthercomprises a cam assembly.
 13. The apparatus of claim 1 wherein thecannula has an outer diameter of approximately 0.032 inches or less. 14.The apparatus of claim 1 wherein the cannula has an outer diameter ofapproximately 0.028 inches or less.
 15. The apparatus of claim 1 whereinthe cannula has a cross-sectional area of approximately 0.0008 squareinches or less.
 16. An apparatus for implanting an ocular implant at alocation in a patient's eye, comprising: an elongate housing having alongitudinal axis; a cannula extending longitudinally from the housing,the cannula having a lumen extending therethrough; a push rod receivedwithin the cannula lumen and in engagement with the implant, the plungermoveable from a first to second position; and a linkage having amoveable end connected to the push rod, and a fixed end secured to thehousing, an actuating lever having a first end pivotally mounted withinthe housing, and a second end in engagement with the linkage, whereinmovement of the second end of the actuating lever against the linkage ina direction normal to the housing axis causes translational movement ofthe moveable end of the linkage from a first to second position parallelto the housing axis, thereby moving the push rod from the first to thesecond position and ejecting the implant from the cannula.
 17. Theapparatus of claim 16 further comprising an ocular implant locatedwithin the lumen cannula.
 18. The apparatus of claim 17 wherein saidimplant is a microimplant.
 19. The apparatus of claim 16 wherein saidactuating lever further comprises a button extending from the housingfor manual depression of the lever.
 20. The apparatus of claim 16wherein the cannula has an outer diameter of 0.032 inches or less. 21.The apparatus of claim 16 wherein the cannula has an outer diameter ofapproximately 0.028 inches or less.
 22. The apparatus of claim 16wherein the cannula lumen has a cross-sectional area of 0.0008 squareinches or less.
 23. A method of delivering an ocular implant at alocation in a patient's eye using the apparatus of claim 1 or
 16. 24. Amethod of delivering an ocular microimplant at a location in a patient'seye using the apparatus of claim 13 or
 20. 25. A method of delivering anocular implant at a location in a patient's eye using an apparatuscomprising a cannula having a proximal end, a distal sharp end, and alumen extending therethrough, a microimplant received within the lumen,and a push rod received through the proximal end of the cannula, themethod comprising the steps of: (a) puncturing the outer layer of apatient's eye with the cannula and inserting the cannula into apatient's eye to a desired location; (b) moving the push rod from theproximal end of the cannula toward the distal end of the cannula,thereby ejecting the implant from the cannula; and (c) removing thecannula and push rod from the patient's eye.
 26. The method of claim 25wherein said implant is a microimplant.
 27. The method of claim 26wherein said implant is biodegradable.
 28. The method of claim 26wherein the puncture in the patient's eye created by the insertion ofthe cannula in step (a) is self-sealing upon the removal of the cannulain step (c).
 29. The method of claim 26 wherein the cannula has an outerdiameter of 0.032 inches or less.
 30. The method of claim 26 wherein thecannula has an outer diameter of approximately 0.028 inches or less. 31.The method of claim 26 wherein the cannula lumen has a cross-sectionalarea of 0.0008 square inches or less.
 32. The method of any one ofclaims 26-31 wherein the puncturing step (a) further comprises insertingthe cannula into the patient's eye at an angle of 45° or less relativeto the eye surface.
 33. An apparatus for implanting an ocular implant ata location in a patient's eye comprising: a cannula having a lumenextending therethrough configured to receive an ocular implant; andmeans for retaining an implant received within the cannula lumen tominimize inadvertent release of the implant from the cannula.
 34. Theapparatus of claim 33 wherein the retention means comprises a frictionalstop which extends into the cannula lumen for contacting an implantreceived therein.
 35. The apparatus of claim 34 wherein the frictionalstop comprises an O-ring, at least a portion of which extends into thecannula lumen for contacting an implant received therein.
 36. Theapparatus of claim 35 wherein the cannula includes a notch, the notchproviding for communication between the cannula lumen and cannulaexterior, and wherein the O-ring is positioned around the cannula andwhere a portion of the O-ring is received in the notch and extends intothe lumen.
 37. The apparatus of claim 34 wherein the cannula includes anotch, the notch providing for communication between the cannula lumenand cannula exterior, and wherein the frictional stop comprises tubingpositioned around the cannula and where a portion of the tubing isreceived in the notch and extends into the lumen.
 38. The apparatus ofclaim 34 wherein the frictional stop comprises a spring mechanism. 39.The apparatus of claim 34 wherein the frictional stop is integral to thecannula.
 40. The apparatus of claim 33 wherein the retention meanscomprises a biocompatible adhesive for adhering the implant to thelumen.
 41. The apparatus of claim 33 wherein the retention meanscomprises a frictional coating applied to the cannula lumen.
 42. Theapparatus of claim 33 wherein the retention means comprises a breakablemembrane deployed within the cannula lumen.